The Late Effects of Radiation Therapy on Skeletal Muscle Morphology and Progenitor Cell Content are Influenced by Diet-Induced Obesity and Exercise Training in Male Mice

Radiation exposure during muscle development induces long-term decrements to skeletal muscle health, which contribute to reduced quality of life in childhood cancer survivors. Whether the effects of radiation on skeletal muscle are influenced by relevant physiological factors, such as obesity and exercise training remains unknown. Using skeletal muscle from our previously published work examining the effects of obesity and exercise training on radiation-exposed bone marrow, we evaluated the influence of these physiological host factors on irradiated skeletal muscle morphology and cellular dynamics. Mice were divided into control and high fat diet groups with or without exercise training. All mice were then exposed to radiation and continued in their intervention group for an additional 4 weeks. Diet-induced obesity resulted in increased muscle fibrosis, while obesity and exercise training both increased muscle adiposity. Exercise training enhanced myofibre cross-sectional area and the number of satellite cells committed to the myogenic lineage. High fat groups demonstrated an increase in p-NFĸB expression, a trend for a decline in IL-6 , and increase in TGFB1 . These findings suggest exercise training improves muscle morphology and satellite cell dynamics compared to diet-induced obesity in irradiated muscle, and have implications for exercise interventions in cancer survivors.